One of the problems associated with topical medical treatment with high potency drugs is in the application of the composition. Most compositions intended for dermatological treatment of the skin are based on cream, ointment of gel vehicles and, when these are applied to the skin, the incidence of extralesional treatment can be substantial; areas surrounding the lesion to be treated as well as the fingers used to apply a product can be affected by the drug.
By using stick compositions having higher viscosities, which can be housed within a protective package, such extralesional treatment can be avoided or at least substantially eliminated. Another advantage of stick formulations is that, by their use, it is simple to achieve a uniform distribution of drug over the lesion to be treated.
Stick based products are not novel in the treatment of skin conditions and several active compounds have been formulated into sticks. Stick compositions, as herein referred to, are formed from erodible, usually soft and waxy materials having a solid consistency. When rubbed across the skin, such compositions are eroded and deposit a coating of their constituent material on the skin. Generally, stick compositions include mixtures of lipids and surfactants as carriers.
A major drawback of those stick compositions used today, however, results from the fact that many drugs, at best, are only marginally soluble in their lipid based formulations and, therefore, must be incorporated into stick compositions as suspended solid particles. This, however, leads to several disadvantages, the most serious one being sedimentation of the active ingredient during manufacture. The method used to manufacture stick compositions involves heating, mixing, packing and cooling and, during, the heating, mixing and cooling steps, the viscosity of the lipid mixture can be sufficiently low to allow the suspended active drug to settle. The resulting sedimentation of the active ingredient reduces the homogeneity of the composition and can prevent the product from meeting the standards required for pharmaceutical products.
Several solutions to the sedimentation problem have been proposed. Some are based on mechanical measures, which involve regularly turning any vessel used to accomodate the composition before it has set, so that the drug particles are maintained in a suspended state. Others involve the addition of thickening agents to form thixotropic gels. None of these proposals, however, have enabled the manufacture of homogeneous formulations in a reproducible way.
Another disadvantage with topical formulations in general, and stick formulations in particular, is the poor bioavailability of the active drug to the skin. For topical dermatological formulations containing corticosteroides, bioavailability can be in the order of a few percent. Low bioavailability has many implications. One is that the effect of a drug can be variable and non-reproducible, both at the site of application and systemically. Another is that, when conditions at the site of application are favourable for the penetration of a drug, systemic concentrations thereof can reach toxic levels.
A corticosteroid stick product containing propylene glycol or 1,3-butylene glycol is previously known from U.S. Pat. No. 4,299,828. However, said product is not based on the use of an unsaturated fatty acid alcohol as a solvent and the alkylene glycols referred to are not utilized as solvents but rather as anti-microbial compounds. Furthermore, it is specifically stated that said anti-microbial compound is not dissolved in the stick but dispersed therein (col 3 lines 35–40 and claim 1), i.e. the stick is not a homogeneous product. In addition thereto the preferred percentage of the alkylene glycol is disclosed as 2–10 and optionally 3–8% by weight (col 3 lines 20–22 and claim 1). Thus, the purpose of the alkylene glycol is completely different from that of the present invention where higher percentages of alkylene glycol have been found to give other effects than those referred to in U.S. Pat. No. 4,299,828.